Nickel(2+) propionate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

In the publication there are no information about replications and the purity of the test substance given.

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity of various chemicals including nickel and cobalt compounds in cultured mouse FM3A cells

Author:

Morita, H., M. Umeda, and H.I. Ogawa

Year:

1991

Bibliographic source:

Mutation Research. 261:131-137.

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test using the Hprt and xprt genes)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Nakamura et al.

Version / remarks:

Year: 1983 (unclear if "Year of test guideline" or "Year of study completion".)

GLP compliance:

not specified

Type of assay:

in vitro mammalian cell gene mutation test using the Hprt and xprt genes

Test material

Test material information

Constituent 1

Reference substance name:

Nickel di(acetate)

EC Number:

206-761-7

EC Name:

Nickel di(acetate)

Cas Number:

373-02-4

Molecular formula:

C2H4O2.1/2Ni

IUPAC Name:

nickel(2+) diacetate

Specific details on test material used for the study:

- Reported as Ni(CH3COO)2-4H2O
- Source: Wako Pure Chemical Industries

Method

Target gene:

HPRT, XPRT

Species / strain

Species / strain / cell type:

mammalian cell line, other: Mouse mammary carcinoma cells (FM3A)

Metabolic activation:

with and without

Metabolic activation system:

2.5 % S15

Test concentrations with justification for top dose:

0, 1.0 x 10e-4, 2.0 x 10e-4, 3.0 x 10e-4, and 4.0 x 10e-4 M

Controls

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Details on test system and experimental conditions:

FM3A cells were exposed to hypoxanthine, aminopterin, and thymidine for 1 week prior to use in the mutation assay, then cultured in Eagle's minimum essential medium supplemented with 3% fetal bovine serum, 1% non-essential amino acids, hypoxanthine, and thymidine. Cultured FM3A cells were then exposed to various concentrations of NiCl2 for 3-48 hours, washed in Hank's balanced salt solution, and then cultured for an additional 7 days. Then, 2 x 10e6 cells were inoculated into 40 mL of selective agar medium containing 10 µg/mL 6-thioguanine (6-TG) and cultured for 14 days. The number of 6TG colonies were counted and mutation frequency (per 10e6 surviving cells) was determined.

Statistics:

Statistical analysis was performed using the Welch test.

Results and discussion

Test results

Key result

Species / strain:

mammalian cell line, other: Mouse mammary carcinoma cells (FM3A)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Additional information on results:

There was a concentration-dependent decrease in percent cell survival following treatment. At 0 M treatment, survival was 76%, with 100% relative plating efficiencies. This decreased to 13% survival with relative plating efficiencies of 18% after treatment at 4.0 x 10e-4 M. The number of mutants per 10e6 surviving cells increased in with Ni exposure, although results were not significant (P<0.05).

Applicant's summary and conclusion

Conclusions:

The test substance was not mutagenic in the in vitro mammalian gene mutation test.